Stem Cell Transplant ComplicationsKIR-STANNCT04882605
KIR Sequencing and Typing for Allograft in Nancy
An observational study of Stem Cell Transplant Complications, run by Central Hospital, Nancy, France.
Trial summary
The use of haploidentical donors for aHSCT has greatly increased this past decade leading to a major paradigm shift: while finding 10/10 HLA-matched donors represented the prior difficulty for decades, the current problem is about finding the best haploidentical donor among several potential ones. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Stem Cell Transplant Complications
- What is being tested?
- MHC typing, KIR typing and Assessment of KIR-based prediction scores
- How many people
- 156 participants
- Where
- No sites listed yet
- Study dates
- 23 Mar 2015to 25 Jul 2019
- How long will I take part?
- 4 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Two independents cohorts of D/R couples (i) Matched siblig donors (MSD) couples : 50 couples selected from the French national database CRYOSTEM (ii) Haploidentical donors couples: exhaustive local cohort of haploidentical HSCT performed in the Hematology Department of Nancy's University Hospital, Lorraine, France. French Minister registration number : DC-2020-4068
COHORT 1 = Matched Sibling Donors couples (MSD couples) INCLUSION CRITERIA
- recipient of HSCT selected from the French national database CRYOSTEM
- adult patients (18-50 years old)
- transplanted in first remission
- receiving myeloablative conditioning without anti-thymoglobulin
- 16 couples without any sign of GVH (8 males and 8 females)
- 16 couples with aGVH without cGVH
- 9 couples with cGVH without aGVH
- 9 couples with both cGVH and aGVH. EXCLUSION CRITERIA
- insufficient DNA material after Miltenyi extraction
COHORT 2 = Haploidentical couples INCLUSION CRITERIA
- patient undergoing a haploidentical HSCT in the Hematology Department of Nancy's University Hospital, Lorraine, France (French Minister registration number : DC-2020-4068) EXCLUSION CRITERIA
- insufficient DNA material after Miltenyi extraction (7 MSD couples)
About this study
Official title: Application of the Major Predictive Scoring Strategies Assessing KIR-based NK Alloreactivity to Donor/Recipient Couples
The use of haploidentical donors for aHSCT has greatly increased this past decade leading to a major paradigm shift: while finding 10/10 HLA-matched donors represented the prior difficulty for decades, the current problem is about finding the best haploidentical donor among several potential ones. The prediction of NK cells alloreactivity toward leukemic cells provides promising perspectives, although the underlying biological processes remain unclear. To date, many prediction models based on KIR and MHC genotyping have been designed and used across studies, which contribute to blur clinical conclusions.
The investigators hypothesized that the diversity of models used to predict NK alloreactivity in aHSCT could partly be responsible for the current literature discrepancies. The main objective of this work consisted of applying the major KIR-based prediction models in D/R couples undergoing aHSCT in different fashions - with MSD and haploidentical donors - to describe their heterogeneity and potential correlations. As clinical data were available for these two cohorts, the investigators described correlations that could be assessed between the scoring strategies and the clinical outcomes.
Read more
As suspected, it was highlighted that the different scoring strategies greatly impact the assessment of alloreactivity within D/R couples. As an example, two broadly used scoring strategies - educational models and missing-ligand models - show clear opposite predictions. Moreover, some scoring strategies seem to be better adapted to genoidentical or haploidentical cohorts, whereas others are robust across the different cohorts. Concerning the clinical-biological correlations, it was highlighted that (i) each scoring strategy is differentially associated to the different outcomes (ii) the different scoring strategies predict one particular outcome with different efficacy (iii) the D/R compatibility greatly impacts the pertinence of the scoring strategy.
This work therefore contributes to unravel the KIR-based alloreactivity prediction of NK cells in aHSCT. This would help to overcome the current literature discrepancies in this field as in making new hypotheses to better understand and predict NK alloreactivity to further develop its use in medical practice.
- Conditions
- Stem Cell Transplant Complications
- Being tested
- MHC typing, KIR typing, Assessment of KIR-based prediction scores
- Keywords
- Hematopoietic Stem Cell Transplantation, acute Graft versus Host Disease, chronic Graft versus Host Disease, Killer Immunoglobulin-like Receptors, NK-mediated alloreactivity
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MHC typingGenetic
Allelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology.
KIR typingGenetic
Allelic genotyping resolution of all 13 KIR genes (KIR2DL1, KIR2DL2/2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS3/2DS5, KIR2DS4, KIR3DL1/3DS1, KIR3DL2, KIR3DL3), 2 KIR pseudogenes (KIR2DP1 and -3DP1) using Illumina technology.
Assessment of KIR-based prediction scoresGenetic
Compiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores
| Study group | Role | What they receive |
|---|---|---|
| Donor/recipient couple with Matched Sibling Donor | Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation
+ its 10/10 HLA-matched donor recruited among his siblings Receives: Genetic: MHC typing; Genetic: KIR typing; Genetic: Assessment of KIR-based prediction scores | |
| Donor/recipient couple with Haploidentical Donor | Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation
+ its 5/10 HLA-matched donor recruited among his relatives Receives: Genetic: MHC typing; Genetic: KIR typing; Genetic: Assessment of KIR-based prediction scores |
What is being measured
The primary outcome is the main question the study is designed to answer.
Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity
Measured: At inclusion
Describe the potential correlations between a KIR-based prediction models and post-allograft outcomes
Measured: at least 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2021
- Study start23 Mar 2015
- Primary completion25 Jul 2019
- Study completion25 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stem Cell Transplant ComplicationsStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 156 participants (actual)
- Target duration
- 4 Months
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cambridge
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04882605
- Sponsor's protocol ID
- 2020PI142
- Acronym
- KIR-STAN
- Status last verified
- May 2021
- First submitted
- 4 May 2021
- Last updated
- 12 May 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Application of the Major Predictive Scoring Strategies Assessing KIR-based NK Alloreactivity to Donor/Recipient Couples
- ClinicalTrials.gov ID
- NCT04882605
- Acronym / sponsor ID
- KIR-STAN / 2020PI142
- Conditions
- Stem Cell Transplant Complications
- Keywords
- Hematopoietic Stem Cell Transplantation, acute Graft versus Host Disease, chronic Graft versus Host Disease, Killer Immunoglobulin-like Receptors, NK-mediated alloreactivity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Collaborators
- University of Cambridge
- Study start
- 23 Mar 2015 (actual)
- Primary completion
- 25 Jul 2019 (actual)
- Study completion
- 25 Jul 2019 (actual)
- First posted
- 12 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The use of haploidentical donors for aHSCT has greatly increased this past decade leading to a major paradigm shift: while finding 10/10 HLA-matched donors represented the prior difficulty for decades, the current problem is about finding the best haploidentical donor among several potential ones. The prediction of NK cells alloreactivity toward leukemic cells provides promising perspectives, although the underlying biological processes remain unclear. To date, many prediction models based on KIR and MHC genotyping have been designed and used across studies, which contribute to blur clinical conclusions.
The investigators hypothesized that the diversity of models used to predict NK alloreactivity in aHSCT could partly be responsible for the current literature discrepancies. The main objective of this work consisted of applying the major KIR-based prediction models in D/R couples undergoing aHSCT in different fashions - with MSD and haploidentical donors - to describe their heterogeneity and potential correlations. As clinical data were available for these two cohorts, the investigators described correlations that could be assessed between the scoring strategies and the clinical outcomes.
As suspected, it was highlighted that the different scoring strategies greatly impact the assessment of alloreactivity within D/R couples. As an example, two broadly used scoring strategies - educational models and missing-ligand models - show clear opposite predictions. Moreover, some scoring strategies seem to be better adapted to genoidentical or haploidentical cohorts, whereas others are robust across the different cohorts. Concerning the clinical-biological correlations, it was highlighted that (i) each scoring strategy is differentially associated to the different outcomes (ii) the different scoring strategies predict one particular outcome with different efficacy (iii) the D/R compatibility greatly impacts the pertinence of the scoring strategy.
This work therefore contributes to unravel the KIR-based alloreactivity prediction of NK cells in aHSCT. This would help to overcome the current literature discrepancies in this field as in making new hypotheses to better understand and predict NK alloreactivity to further develop its use in medical practice.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 4 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donor/recipient couple with Matched Sibling Donor | – | Genetic: MHC typing, Genetic: KIR typing, Genetic: Assessment of KIR-based prediction scoresDonor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation + its 10/10 HLA-matched donor recruited among his siblings |
| Donor/recipient couple with Haploidentical Donor | – | Genetic: MHC typing, Genetic: KIR typing, Genetic: Assessment of KIR-based prediction scoresDonor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation + its 5/10 HLA-matched donor recruited among his relatives |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Two independents cohorts of D/R couples (i) Matched siblig donors (MSD) couples : 50 couples selected from the French national database CRYOSTEM (ii) Haploidentical donors couples: exhaustive local cohort of haploidentical HSCT performed in the Hematology Department of Nancy's University Hospital, Lorraine, France. French Minister registration number : DC-2020-4068
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MHC typingAllelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology. | Genetic | Donor/recipient couple with Haploidentical Donor, Donor/recipient couple with Matched Sibling Donor |
| KIR typingAllelic genotyping resolution of all 13 KIR genes (KIR2DL1, KIR2DL2/2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS3/2DS5, KIR2DS4, KIR3DL1/3DS1, KIR3DL2, KIR3DL3), 2 KIR pseudogenes (KIR2DP1 and -3DP1) using Illumina technology. | Genetic | Donor/recipient couple with Haploidentical Donor, Donor/recipient couple with Matched Sibling Donor |
| Assessment of KIR-based prediction scoresCompiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores | Genetic | Donor/recipient couple with Haploidentical Donor, Donor/recipient couple with Matched Sibling Donor |
Primary outcome
Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity
Time frame: At inclusion
Describe the potential correlations between a KIR-based prediction models and post-allograft outcomes
Time frame: at least 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Stem Cell Transplant Complications, run by Central Hospital, Nancy, France.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity (time frame: At inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.